Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/8560
Title: Structural insights of SIR2rp3 proteins as promising biotargets to fight against Chagas disease and leishmaniasis
Authors: Sacconnay, Lionel
Smirlis, Despina
Queiroz, Emerson Ferreira
Wolfender, Jean-Luc
Soares, Milena Botelho Pereira
Carrupta, Pierre-Alain
Nurisso, Alessandra
Affilliation: University of Geneva. University of Lausanne. Pharmacochemistry and Phytochemistry & Bioactive Natural Products. School of Pharmaceutical Sciences. Geneva, Switzerland
Hellenic Pasteur Institute. Laboratory of Molecular Parasitology. Microbiology Dept. Athens, Greece
University of Geneva. University of Lausanne. Pharmacochemistry and Phytochemistry & Bioactive Natural Products. School of Pharmaceutical Sciences. Geneva, Switzerland
University of Geneva. University of Lausanne. Pharmacochemistry and Phytochemistry & Bioactive Natural Products. School of Pharmaceutical Sciences. Geneva, Switzerland
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Salvador, BA, Brazil
University of Geneva. University of Lausanne. Pharmacochemistry and Phytochemistry & Bioactive Natural Products. School of Pharmaceutical Sciences. Geneva, Switzerland
University of Geneva. University of Lausanne. Pharmacochemistry and Phytochemistry & Bioactive Natural Products. School of Pharmaceutical Sciences. Geneva, Switzerland
Abstract: Trypanosoma cruzi and Leishmania spp. are protozoan pathogens responsible for Chagas disease and leishmaniasis, respectively. Current therapies rely only on a very small number of drugs, most of them are inadequate because of their severe host toxicity or drug-resistance phenomena. In order to find therapeutic alternatives, the identification of new biotargets is highly desired. In this study, homology modelling, docking and molecular dynamics simulations have been used to generate robust 3D models of NAD(+)-dependent deacetylases from Trypanosoma and Leishmania spp., known as SIR2rp3, whose structures have never been described before. Molecular docking of known inhibitors revealed strong analogies with the mitochondrial human SIRT5 in terms of binding mode and interaction strength. On the other hand, by extending the analysis to the channel rims, regions of difference between host and parasitic targets, useful for future selective drug design projects, were pointed out.
DeCS: Inibidores Enzimáticos/química
Modelos Moleculares
Sirtuína 2/química
Sequência de Aminoácidos
Doença de Chagas
Inibidores Enzimáticos/farmacologia
Humanos
Leishmaniose
Proteínas Mitocondriais/antagonistas & inibidores
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
Dados de Sequência Molecular
Conformação Proteica
Alinhamento de Sequência
Sirtuína 2/antagonistas & inibidores
Trypanosoma cruzi/metabolismo
Issue Date: 2013
Publisher: The Royal Society of Chemistry
Citation: SACCONAY, L. et al. Structural insights of SIR2rp3 proteins as promising biotargets to fight against Chagas disease and leishmaniasis. Molecular Biosysttems, v. 9, n. 9, p. 2223-2230, 2013.
DOI: 10.1039/c3mb70180h
ISSN: 1742-2051
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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